{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:09:49Z","timestamp":1792552189577,"version":"4.5.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A growing body of evidence underscores a significant association between neurological disorders, particularly migraines, and the gut microbiota. However, a research gap persists in understanding the cause-and-effect dynamics between these elements. Therefore, we employed robust methodologies aimed at thoroughly exploring the causal relationship between the gut microbiome and migraines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Employing bidirectional Two Sample Mendelian Randomization (TSMR) analysis, we investigated the causal association between the composition of the gut microbiota and migraines. Data summarizing the relationship between gut microbiota and migraines were extracted from one or more genome-wide association studies. The TSMR analysis employed five methods to assess the correlation between the gut microbiota and migraines, with the inverse variance-weighted method serving as the primary approach for analyzing causal links. Sensitivity analyses were applied to address horizontal pleiotropy and heterogeneity. Simultaneously, a meta-analysis was performed to strengthen the robustness of the findings. Additionally, a reverse TSMR was carried out to explore potential occurrences of reverse causal relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The ongoing TSMR analysis identified a collection of 14 bacterial taxa connected to migraines. Among these, 8 taxa exhibited a protective effect, while 5 taxa had a detrimental impact, and 1 taxon maintained a neutral relationship. The reverse Mendelian randomization analysis highlighted stable outcomes for only one bacterial taxonomic group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study confirms a causal relationship between the gut microbiota and migraines, offering a new perspective for migraine research. Strategically targeting specific bacterial taxa with dysregulation may be effective in both preventing and treating migraines, thus opening new avenues for therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1356974","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T15:31:13Z","timestamp":1719934273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A thorough investigation into the correlation between migraines and the gut microbiome: an in-depth analysis using Mendelian randomization studies"],"prefix":"10.3389","volume":"15","author":[{"given":"Xuege","family":"Zang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkun","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengshu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s10194-016-0699-5","article-title":"GBD 2015: migraine is the third cause of disability in under 50s","volume":"17","author":"Steiner","year":"2016","journal-title":"J Headache Pain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s10194-018-0846-2","article-title":"Migraine is first cause of disability in under 50s: will health politicians now take notice?","volume":"19","author":"Steiner","year":"2018","journal-title":"J Headache Pain"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The international classification of headache disorders, 3rd edition (beta version)","volume":"33","year":"2013","journal-title":"Cephalalgia"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(19)30185-1","article-title":"Migraine and the trigeminovascular system-40 years and counting","volume":"18","author":"Ashina","year":"2019","journal-title":"Lancet Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1212\/WNL.0b013e3182a6cb72","article-title":"Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine","volume":"81","author":"Cernuda-Moroll\u00f3n","year":"2013","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0140-6736(79)92692-8","article-title":"Neurotransmitters and the fifth cranial nerve: is there a relation to the headache phase of migraine?","volume":"2","author":"Moskowitz","year":"1979","journal-title":"Lancet"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1046\/j.1468-2982.2000.00146.x","article-title":"Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in internal jugular vein blood during spontaneous migraine attacks","volume":"20","author":"Sarchielli","year":"2000","journal-title":"Cephalalgia"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/j.1468-2982.2007.01486.x","article-title":"Comorbidity of headache and gastrointestinal complaints. 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